18F-Labelled FVIIa Imaging Agent for Tissue Factor PET
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Solution Overview
Problem
Current methods for noninvasive imaging of Tissue Factor expressing tumors are limited, particularly in humans, due to high background signals from normal tissues, which complicates the diagnosis and monitoring of cancer progression and treatment response.
Innovation Solution
Development of a positron-emitting 18-F labelled active site inhibited factor VIIa (FVIIai) imaging agent, administered in doses of 50-400 MBq, for PET imaging of Tissue Factor expressing tumors, utilizing native human FVIIa or variants radiolabeled with 18-F, which provides clear diagnostic images through SUVmax and SUVmean quantification.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional imaging agents are used for noninvasive imaging of Tissue Factor expressing tumors, then tumor detection is possible, but background signals from normal tissues are high which complicates diagnosis and monitoring
Solution Approach 1:
The patent extracts and eliminates the harmful background signal component by using an active site inhibited FVIIa variant that specifically binds to TF-expressing tumors while avoiding non-specific binding to normal tissues. The radiolabeled inhibitor selectively targets the tumor tissue, effectively separating the tumor signal from the background noise of normal tissues.
Solution Approach 2:
The patent changes the chemical and biological parameters of the imaging agent by using a radiolabeled active site inhibited FVIIa variant with modified binding characteristics. This parameter change enables selective accumulation in TF-expressing tumors while reducing background uptake in normal tissues, thereby improving the signal-to-noise ratio for tumor detection.
2Reliability
If TF-targeting therapies are developed, then treatment effectiveness is improved, but the need for accurate companion diagnostics increases to monitor treatment response
Solution Approach 1:
The radiolabeled active site inhibited FVIIa variant serves multiple functions: it acts as both a diagnostic imaging agent for detecting TF-expressing tumors and as a companion diagnostic for monitoring treatment response to TF-targeting therapies. This multi-functionality simplifies the overall diagnostic workflow while maintaining high reliability for treatment evaluation.
Solution Approach 2:
The imaging agent provides real-time feedback on TF expression levels and treatment response through quantitative PET imaging. By measuring the uptake of the radiolabeled inhibitor, clinicians can monitor whether TF-targeting therapies are effectively reducing TF expression, enabling dynamic adjustment of treatment strategies based on actual treatment response.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The 18-F labelled FVIIai agent effectively reduces background signals, allowing for accurate visualization and quantification of tumor Tissue Factor expression, enabling reliable diagnosis, treatment monitoring, and companion diagnostics for emerging TF-targeting therapies, particularly in cancers like breast, gastric, esophageal, liver, and pancreatic cancer.
Implementation Method 1
positron-emitting 18-F labelled active site inhibited factor VIIa (FVIIai) imaging agent
Implementation Method 2
native human FVIIa or a variant thereof radiolabeled with 18-F
Implementation Method 3
The zymogen FVII gets activated to the serine protease, FVIIa; and the TF:FVIIa complex further activates factor X
Data Source
Figure 1A~1B
Figure 2
Figure 3
AI summary
There is provided a positron-emitting 18F-labelled Factor VIIfor non-invasive PET imaging of tumor TF expression in humans. More specifically the invention relates to human TFPET imaging of pancreaticcancer metastasis for diagnosis, staging, treatment monitoring and especially as an imaging biomarker for predicting prognosis, progression and recurrence.